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| Profile Name | STK11 Q37* |
| Gene Variant Detail | |
| Relevant Treatment Approaches | mTOR Inhibitor mTORC1 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| STK11 mutant | lung non-small cell carcinoma | sensitive | Gedatolisib | Preclinical | Actionable | In a preclinical study, Gedatolisib (PF-05212384) inhibited growth of human non-small cell lung carcinoma cells harboring an STK11 mutation in culture (PMID: 21325073). | 21325073 |
| STK11 inact mut | endometrial cancer | sensitive | Sirolimus | Preclinical | Actionable | In a preclinical study, Rapamune (sirolimus) reduced S6K phosphorylation and inhibited tumor growth in mouse models of STK11 (LKB1)-deficient endometrial cancer, including models with advanced tumors (PMID: 20142330). | 20142330 |
| STK11 inact mut | Advanced Solid Tumor | sensitive | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the presence of an STK11 inactivating mutation and STK11 loss expression signature was associated with increased sensitivity to Selumetinib (AZD6244) in human tumor cell lines in culture (PMID: 27821489). | 27821489 |
| STK11 inact mut | Advanced Solid Tumor | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the presence of an STK11 loss expression signature, which correlated to STK11 inactivating mutations, was associated with increased sensitivity to Mekinist (trametinib) in human tumor cell lines in culture (PMID: 27821489). | 27821489 |
| STK11 inact mut | lung non-small cell carcinoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, non-small cell lung cancer cell lines harboring STK11 inactivating mutations demonstrated increased sensitivity to Mekinist (trametinib) in culture (PMID: 27821489). | 27821489 |
| STK11 inact mut | Advanced Solid Tumor | sensitive | Refametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the presence of an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to Refametinib (BAY86-9766) in human tumor cell lines in culture (PMID: 27821489). | 27821489 |
| STK11 inact mut | Advanced Solid Tumor | sensitive | CI-1040 | Preclinical - Cell culture | Actionable | In a preclinical study, the presence an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to CI-1040 (PD184352) in human tumor cell lines in culture (PMID: 27821489). | 27821489 |
| STK11 inact mut | Advanced Solid Tumor | sensitive | PD-0325901 | Preclinical - Cell culture | Actionable | In a preclinical study, the presence of an STK11 loss expression signature, which correlates with STK11 inactivating mutations, was associated with increased sensitivity to PD-0325901 in human tumor cell lines in culture (PMID: 27821489). | 27821489 |
| STK11 mutant | lung non-small cell carcinoma | decreased response | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant STK11 correlated with a worse outcome with immune checkpoint inhibitor treatment compared to wild-type STK11 in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... |
| STK11 mutant | stomach cancer | not applicable | N/A | Guideline | Risk Factor | Germline mutations in STK11 result in Peutz Jeghers syndrome, which is associated with increased risk of developing gastric cancer (NCCN.org). | detail... |
| STK11 mutant | pancreatic cancer | not applicable | N/A | Guideline | Risk Factor | Germline mutations in STK11 result in Peutz Jeghers syndrome, which is associated with increased risk of developing pancreatic cancer (NCCN.org). | detail... |
| STK11 mutant | lung non-small cell carcinoma | decreased response | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, mutant STK11 correlated with a worse outcome with immune checkpoint inhibitor treatment compared to wild-type STK11 in non-small cell lung cancer patients (Ann Oncol 2017, Vol 28, Suppl 5, Abstract #1138PD). | detail... |
| STK11 mutant | small intestine adenocarcinoma | not applicable | N/A | Guideline | Risk Factor | Peutz-Jeghers syndrome often results from mutations in the STK11 gene, and is associated with increased risk of developing small bowel adenocarcinoma (NCCN.org). | detail... |
| STK11 mutant | lung non-squamous non-small cell carcinoma | predicted - sensitive | Camrelizumab + Rivoceranib | Phase Ib/II | Emerging | In a Phase Ib/II trial, non-squamous NSCLC patients harboring STK11 and/or KEAP1 mutations (n=14) demonstrated an improved 12-month survival rate (85.1% vs 53.1%; p=0.01), and a trend towards improved objective response rate (42.9% vs 28.1%; p=0.33), disease control rate (92.9% vs 65.6%, p=0.053), and median progression-free survival (9.4 vs 5.3 months; p=0.64) compared to wild-type STK11/KEAP1 patients (n=32) treated with Camrelizumab (SHR-1210) plus Rivoceranib (apatinib) (PMID: 33323401; NCT03083041). | 33323401 |
| STK11 mutant | lung adenocarcinoma | not predictive | unspecified PD-1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, lung adenocarcinoma patients harboring an STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type STK11 when treated with an unspecified PD-1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). | 32312757 |
| STK11 mutant | lung adenocarcinoma | not predictive | unspecified PD-L1 antibody | Clinical Study - Cohort | Actionable | In a clinical study, lung adenocarcinoma patients harboring an STK11 mutation demonstrated a shorter progression free survival compared to patients with wild-type STK11 when treated with an unspecified PD-L1 antibody treatment, but when compared to other treatments, all were associated with shorter progression free survival (PMID: 32312757). | 32312757 |
| STK11 mutant | lung adenocarcinoma | not applicable | N/A | Clinical Study | Emerging | In clinical studies, STK11 mutations were associated with an inferior prognosis in patients with lung adenocarcinoma (PMID: 32312757, PMID: 32413741). | 32413741 32312757 |
| STK11 inact mut | lung non-squamous non-small cell carcinoma | no benefit | Avelumab + Talazoparib | Phase II | Actionable | In a Phase II trial (SWOG S1900C, LUNG-MAP sub-study), Talzenna (talazoparib) and Bavencio (avelumab) combination therapy did not meet the efficacy threshold in patients with advanced or recurrent non-squamous non-small cell lung cancer harboring STK11 pathogenic mutations or biallelic loss, resulting in an objective response rate of 2% (1/47) and a disease control rate at 12 weeks of 40% (17/47) (J Clin Oncol 40, no. 16_suppl (June 01, 2022) 9060; NCT04173507). | detail... |
| STK11 inact mut | lung adenocarcinoma | predicted - sensitive | Everolimus | Case Reports/Case Series | Actionable | In a Phase II trial, Afinitor (everolimus) treatment resulted in a complete response lasting more than 10 months in a heavily pre-treated patient with lung adenocarcinoma harboring 2 in cis non-coding STK11 mutations (STK11 c.375-2del and c.375-G>C), (PMID: 34422335; NCT02352844). | 34422335 |
| STK11 mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline STK11 mutations are associated with increased risk of developing breast cancer (NCCN.org). | detail... |